Primary biliary cirrhosis (PBC) appears to be a model autoimmune disease. Abnormal immune mechanisms are being studied in this disease, but so far a disease-specific immunologic deficit has not been defined with certainty. To determine whether previously described abnormalities of lymphocyte function in PBC might be due to altered function of immunoregulatory T cell subpopulations, phenotypic and functional characteristics of T cells that have the CD4 antigen detectable (by monoclonal antibody) on their surface were examined. Patients with PBC were found to have normal numbers of CD4+, Leu-8+ T cells, but, in contrast to patients with other liver diseases, suppression of immunoglobulin synthesis and mitogen-stimulated proliferation mediated by this subpopulation of T cells were defective. These defects in the function of CD4+, Leu-8+ T cells in patients with PBC were corrected by phorbol ester suggesting that abnormal function of the biochemical pathway involving protein kinase C may contribute to the immunological abnormalities exhibited by patients with PBC. In contrast to control patients with non-PBC chronic inflammatory liver diseases, mRNA for IL-1,2,4,5 and 6, IFN-gamma and TNF-alpha were not detected in liver biopsies from patients with PBC. While these findings do not exclude a role for cytokines in the mediation of the bile duct lesions in PBC, they suggest that immunologic injury that is not mediated by cytokines plays a major role in disease progression in PBC.